The ability to simply and reproducibly produce a highly labeled nucleic acid probe is a very important aspect for the large group of molecular biology and DNA diagnostic applications that involve a hybridization reaction. Yet to date, there is not an easy way to produce a highly labeled probe that is optimal for a wide range of applications. We have used a rational approach to design a series of non-radioactive labeling reagents that should alleviate many of the shortcomings of the currently used labeling protocols. These new labeling reagents are designed to covalently attach any one of four common non-radioactive detectable labels to any nucleic acid. The proposed labeling procedures are one- step, efficient, and should create labeled nucleic acids that are stable long term. Given their ease of use and high efficiency, the labeling will be of great utility in a wide variety of molecular and cellular biological studies and have huge commercial potential. PROPOSED COMMERCIAL APPLICATION: This new method of non-radioactive nucleic acid labeling will be commercialized by: (1) selling the technology in the form of reagent kits to biomedical and basic researchers (2) licensing the technology to pharmaceutical companies for diagnostic purposes.